Epidemics of enterically transmitted non-A, non-B hepatitis (hepatitis E) have been reported in Asia, Africa, and North America but not in the United States or Canada. Similar cases of sporadic hepatitis, presumed to be hepatitis E, account for up to 90% of reported acute hepatitis in countries where hepatitis E is endemic. Hepatitis E virus (HEV) has been implicated in fulminant hepatitis of pregnancy. This disease has a 20% fatality rate. That a viral agent was responsible for hepatitis E epidemics was first shown in 1983. The genome of HEV consists of a single strand of positive sense RNA that contains 3 open reading frames (ORFs). ORF1 encodes nonstructural proteins, ORF2 encodes the principal capsid protein, and ORF3 encodes a protein of unknown function. The goal of this project is to characterize HEV, to determine the extent and pattern of its involvement in enterically transmitted hepatitis, and to develop a vaccine for the prevention of hepatitis E.